Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fluorine-containing building blocks have been developed [21][22][23][24][25]. Jubault and Poisson et al. reported SN2’ reactions of hydride or alcohols to electrophilic fluorine-containing alkenes gave the corresponding fluoroalkenes (Scheme 1B) [21]. In recent years, many fluorine-containing coupling

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• H2 over CO2 becomes crucial for effective CO2 reduction [7]. Additionally, the strength of the interaction between the catalyst and the resulting system after hydride transfer presents a limitation. The formation of a robust LA–oxygen interaction may impede proton transfer to the basic oxygen atom

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• the DDQH• radical to generate a carbocation and DDQH−. In path B, the reaction involves direct hydride transfer to DDQ, forming DDQH− and a carbocation. In both pathways, the amine nucleophile captures the carbocation, resulting in the final amination product after losing a proton. Subsequently, DDQH

• form a cyclic alkyl radical. The alkyl radical is further oxidized by [Co(III)] to produce the target amination product and a [Co(II)–H] species via direct hydrogen transfer or β-hydride elimination. Deprotonation of [Co(II)–H] by MeO− regenerates the [Co(I)] complex, which is subsequently oxidized

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• carried out for the verification of the intermediate leading to the product 11. Although we initially assumed that the epoxy ring opening occurred by hydride generated through the β-elimination of the n-C10H21MgBr-based cuprate species, the TLC analysis of the reaction mixture did not show any evidence of

• well compares with the one by Alexakis et al. [57]. In their instance, the reaction of t-Bu2CuCNLi2 and cyclohexene oxide afforded a mixture of products in 10 and 50% yields as a result of the epoxy ring opening by t-Bu group and hydride, respectively. Their additional experiment to quench the

• corresponding intermediate by D2O proved that no deuteration occurred. This result clearly indicated that hydride was released from the t-Bu group of the Cu(III) species formed after the nucleophilic attack of the epoxy ring. In our case, since the strongly electron-withdrawing CF3 group would render the rate

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• abstraction reaction from tin hydride or hydrosilane by radical initiators such as AIBN has effectively been used. When tin and silyl radicals generated in this way are reacted with isocyanides, they are more susceptible to steric hindrance than group 16 or 15 heteroatom radicals due to the greater number of

• radicals abstract hydrogen from the tin hydride or hydrosilane, and the reduction reaction proceeds with the concomitant formation of stannyl or silyl cyanide 15 as byproducts (Scheme 9a) [38][43]. In the presence of acrylonitrile, the formed alkyl radical can add to acrylonitrile, affording the addition

• with alkenyl, alkynyl, aryl, and isocyano groups as unsaturated groups. Intramolecular cyclization of ortho-alkynylaryl- or ortho-alkenylaryl isocyanides Fukuyama et al. reported that the reaction of an aryl isocyanide with an alkenyl group at the ortho-position with tin hydride in the presence of AIBN

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• 93 (Scheme 33) [116]. The presence of two equivalents of sodium hydride deprotonates the acidic α-NH of arylhydrazine, thereby determining the regioselective attack in addition–elimination sequence furnishing a hydrazine enaminone intermediate, and ultimately leading to pyrazole 93 after cyclization

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• -difluoroethylene was based on 1,2-dichloro-1,2-difluoroethane (HCFC-132) [48][49][50][51][52], prepared from 1,1,2,2-tetrachloro-1,2-difluoroethane (CFC-112) by reduction using lithium aluminum hydride [48][49][50][51] or photoreduction (Scheme 2) [51]. The resulting HCFC-132 reacted with zinc [47][49][52] or

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• Scheme 1 compound 6 was treated with isopropyl iodide (7) in DMF in the presence of sodium hydride to provide products 8 and 9 in 38% and 46% yields, respectively. The structures of both compounds were unambiguously assigned using X-ray crystallography and 1H and nuclear Overhauser effect (NOE) NMR

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• sodium hydride, yielding moderate yields (ranging from 23% to 68%). The cyclization initially formed the non-isolated intermediate i, which was oxidized by molecular oxygen from air, introducing the hydroxy group at the α-position of the cyano group. The protocol utilised mild conditions and short

• reported a novel and straightforward method for synthesizing spiro 2,5-dihydrofuran derivatives starting from 17-ethynyl-17-hydroxysteroids such as lynestrenol (38) (Scheme 12) [25]. The 17-hydroxy group of steroids underwent allylation using allyl bromide and sodium hydride. After formation of the alkenyl

• promoted by the action of sodium hydride, alkylation of the morpholine nitrogen atom on 129 provided a diverse range of compounds (Scheme 36). In 2013, the same reaction sequence was reported by Poirier’s group, resulting in a spiromorpholinone at C-3 position derived from epi-ADT that exhibited activity

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• in unexpected conversions, including the formation of an allylic carbocation at C1, followed by transannular hydride transfer from C8 to afford ketone 20 in 62% yield. With the 5/8/5 tricyclic scaffold 20 in hand, site- and diastereocontrolled C9 hydroxylation of 20 produced a substrate 21 for the

• pentacyclic secondary amine 97 bearing the ester linker in the C1 side chain in one pot. After removal of SfmC by precipitation and centrifugation, the reaction mixture containing secondary amine 97 was subjected to the reductive amination using 2-picoline borane as a hydride source, yielding tertiary amine

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• of a hydride ion from a tetracoordinated intermediate (B), which is formed upon hydroxide addition to the aldehyde (A). The primary pathway of the reaction entails the rate-determining step of hydride ion transfer via either a linear or bent transition state (C) to a second molecule of aldehyde

• transformation of the aryl glyoxals is outlined below (Scheme 4), which depicts the coordination of the hemiacetal B with the metal catalyst to give C, followed by hydride transfer to form the metal-coordinated Cannizzaro product D. Another intramolecular asymmetric Cannizzaro reaction was reported by Wu et al

• in the appropriate vicinity for the reaction to take place in appreciably good yields (84%). The barium cation template is the key for the reaction, as is the base concentration for effective hydride transfer (Scheme 14) [29]. They also extended the scope of the intramolecular Cannizzaro reaction to

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• , C–C, and C–heteroatom bond formations. The best known technique for the creation of alkyl radicals is the homolytic cleavage of the C–X bond of alkyl halides by toxic tin hydride [17]. Later, various efforts have been made to replace toxic tin hydrides with other reagents [33][34][35][36][37][38][39

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• a hydride donor [5][6][7][8]. On the other hand, aryl radical-involved hydroarylation would be a promising alternative for the synthesis of alkylarenes with high anti-Markovnikov selectivity [9][10]. Aryl halides have received increased attention as ideal radical precursors because of their

• intermediates through a single-electron transfer process [26][27][28][29][30][31]. In particular, electroreductive transformations have recently received renewed attention from modern synthetic chemists as a safer protocol than conventional methods using chemical reductants such as metal hydride species [32][33

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• ][11][12]. For example, 2 can be transformed to its dianion 7 by action of two equivalents of LDA or by sequential addition of sodium hydride and n-butyllithium (Scheme 1). In contrast to 2, dianion 7 reacts with electrophiles at its terminal carbon atom. 1,3-Bis(silyloxy)-1,3-butadienes, containing

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• isoprenoid allylic carbocation has the capability to engage in standard carbocation reactions, including cyclization via intramolecular olefin attack at the positively charged center, Wagner–Meerwein rearrangements, and hydride or proton shifts. This sequence concludes either through deprotonation, resulting

• diols by addition of water. For each of these intermediates, simple deprotonation or nucleophilic attack by water are possible. Also, hydride shifts can occur first, which widens the chemical space of possible products. Additionally, the presence of multiple stereocenters adds to the rich

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• to the scientific community [10][11][12]. In this process, first, the metal-catalyzed dehydrogenation of the alcohol provides a reactive substrate for coupling with nucleophiles and the active metal hydride species. Later, the borrowed hydrogen is used in the final step to reduce unsaturated

• aldehydes or ketones, undergo base-assisted condensation reactions with amines providing the corresponding imines. In the last step, the active manganese hydride complexes reduce the imine compounds and afford the desired alkylated amine products (Scheme 2B). Several well-defined manganese complexes have

• indicates that the cation-coordinative interaction with the catalyst plays a significant role. Moreover, the mechanistic investigation suggested that the observed selectivity is due to the more reactive potassium manganate hydride towards the hydrogenation of imines to amines than the sodium manganate

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• palladium(II)–N,N-ligand complex (II), to which the pyrrolidine substrate coordinates (III). Next, migratory insertion takes place generating the alkylpalladium species (IV), which upon a sequence of β-elimination (V) and hydride insertion leads to alkylpalladium intermediate (VI). Finally, upon

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• deoxyconidiogenol (4, Scheme 1A) by several terpene cyclases from fungus (PcCS, PchDS, PrDS) [15][16], which involves a 1,11-10,14 cyclization of GGPP, followed by 1,2-alkyl shift and a 2,10-cyclization, to give the key C3 cationic intermediate IM-1. A key 1,2-hydride shift from C2 to C3, which was observed in the

• IM-7. A key 1,3-hydride shift of IM-7 from the β-face, followed by deprotonation of the formed C2-cation IM-8, would deliver the originally proposed structure 1' [6]. However, no related natural products that would be derived from the intermediates of this pathway have been found so far. A third

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• alkene reactivity is essential. Two reactivity scales for alkenes are available in the literature, one considering the reactivity of the alkene itself (Mayr scale) [25] and the other the stability of the corresponding cation after protonation (hydride affinities) [26]. In the polar hydrochlorination

• . Thermodynamic and theoretical data provide hydride affinities, which correspond to the negative heat of formation for the combination of a hydride anion with a given cation in the gas phase (Figure 2) [26][29]. It is noteworthy that, in contrast to the hydride affinity scale, the Mayr scale considers energetic

• a mixture of E- and Z-octene (67) (Scheme 10). They also mentioned in a footnote that 2-chlorooctane (41) was contaminated by "some 3-chlorooctane” (68). The formation of regioisomers through hydride or alkyl shifts is a common occurrence in hydrochlorination reactions involving secondary cations

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• stereoisomers, ent-CPP and syn-CPP. Class II TCs can also generate further structural diversity through hydride shifts, methyl shifts, and/or skeletal rearrangement of the labdadienyl+ diphosphate intermediate which is formed by the initial bicyclization. Following this class II TC-mediated cyclization, class I

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• , hydride shift process, and photoinduced homolytic cleavage of the C–Pd bond, furnishing hybrid α-ester alkylpalladium radical I. In path b, upon irradiation with blue light, photoexcited Pd(0)Ln* reduces ethyl diazoacetate (1a) to Pd-radical species I by a proton-coupled electron transfer (PCET) process

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• cyanomethyl (7) groups at the 2′-OH. The synthetic routes to compounds 4–9 are shown in Scheme 1. The 2′-OH of adenosine was alkylated with several alkyl halides in the presence of sodium hydride (NaH). Both the 3′-OH and 5′-OH groups of compounds 10a–e were protected by a TBS group, followed by the selective

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• hydride resulted in the formation of the oxepine ring by a double substitution reaction, to yield the desired dinaphthooxepine 33. The non-planar character of dinaphthooxepine bisimides was confirmed by X-ray crystal structure, and stability towards thermal or photoactivation was also established. Cyclic

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• acenaphthylene 8) or as a result of double protodebromination (giving acenaphthene 5). Overall, the observed process resembles a redox transformation. Benzyl-type anions, which have hydride mobility and are formed in an alkaline environment from 15, may act as a reducing agent here. We tried to stop this

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• finally substituted for a hydride derived from NADPH by AvaA7. Interestingly, there are more than 100 BGCs that possess a set of ava gene homologs in the genome database, suggesting that these BGCs are responsible for the biosynthesis of avenalumic acid or its derivatives [13]. In this study, we focused